beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
(2012) In Nature Cell Biology 14(11). p.1169-1180- Abstract
- Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is... (More)
- Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3259641
- author
- Mack, Natalie A. ; Porter, Andrew P. ; Whalley, Helen J. ; Schwarz, Juliane P. ; Jones, Richard C. ; Syed Khaja, Azharuddin Sajid LU ; Bjartell, Anders LU ; Anderson, Kurt I. and Malliri, Angeliki
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Cell Biology
- volume
- 14
- issue
- 11
- pages
- 1169 - 1180
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000310778100010
- scopus:84869085252
- pmid:23103911
- ISSN
- 1465-7392
- DOI
- 10.1038/ncb2608
- language
- English
- LU publication?
- yes
- id
- 16889f79-3dad-4007-bb8c-9500896edef0 (old id 3259641)
- date added to LUP
- 2016-04-01 14:20:34
- date last changed
- 2022-01-28 00:07:34
@article{16889f79-3dad-4007-bb8c-9500896edef0, abstract = {{Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy.}}, author = {{Mack, Natalie A. and Porter, Andrew P. and Whalley, Helen J. and Schwarz, Juliane P. and Jones, Richard C. and Syed Khaja, Azharuddin Sajid and Bjartell, Anders and Anderson, Kurt I. and Malliri, Angeliki}}, issn = {{1465-7392}}, language = {{eng}}, number = {{11}}, pages = {{1169--1180}}, publisher = {{Nature Publishing Group}}, series = {{Nature Cell Biology}}, title = {{beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity}}, url = {{http://dx.doi.org/10.1038/ncb2608}}, doi = {{10.1038/ncb2608}}, volume = {{14}}, year = {{2012}}, }